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These authors contributed equally to this work.
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Research Article
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Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment
Article first published online: 3 AUG 2011
DOI: 10.1002/emmm.201100159
Copyright © 2011 EMBO Molecular Medicine
This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Additional Information
How to Cite
Amar, J., Chabo, C., Waget, A., Klopp, P., Vachoux, C., Bermúdez-Humarán, L. G., Smirnova, N., Bergé, M., Sulpice, T., Lahtinen, S., Ouwehand, A., Langella, P., Rautonen, N., Sansonetti, P. J. and Burcelin, R. (2011), Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med, 3: 559–572. doi: 10.1002/emmm.201100159
Publication History
- Issue published online: 1 SEP 2011
- Article first published online: 3 AUG 2011
- Accepted manuscript online: 4 JUL 2011 03:21AM EST
- Manuscript Accepted: 20 JUN 2011
- Manuscript Revised: 25 MAY 2011
- Manuscript Received: 2 FEB 2011
Funded by
- Italian Telethon Foundation and Cariplo Foundation
- European Commission's Seventh Framework programme. Grant Number: 241913
Keywords:
- Bifidobacterium lactis 420;
- diabetes;
- inflammation;
- obesity;
- pathogen-associated molecular pattern receptors
Abstract
A fat-enriched diet modifies intestinal microbiota and initiates a low-grade inflammation, insulin resistance and type-2 diabetes. Here, we demonstrate that before the onset of diabetes, after only one week of a high-fat diet (HFD), live commensal intestinal bacteria are present in large numbers in the adipose tissue and the blood where they can induce inflammation. This translocation is prevented in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but overtly increased in Myd88 knockout and ob/ob mouse. This ‘metabolic bacteremia’ is characterized by an increased co-localization with dendritic cells from the intestinal lamina propria and by an augmented intestinal mucosal adherence of non-pathogenic Escherichia coli. The bacterial translocation process from intestine towards tissue can be reversed by six weeks of treatment with the probiotic strain Bifidobacterium animalis subsp. lactis 420, which improves the animals' overall inflammatory and metabolic status. Altogether, these data demonstrate that the early onset of HFD-induced hyperglycemia is characterized by an increased bacterial translocation from intestine towards tissues, fuelling a continuous metabolic bacteremia, which could represent new therapeutic targets.